Source: Circulation  |  Posted 9 years ago

Losartan does not alter phenytoin's pharmacokinetics, however, phenytoin does inhibit the conversion of losartan to its active metabolite.

Researchers from the University of North Carolina at Chapel Hill, United States, compared the pharmacokinetics of cytochrome P450 (CYP) 2C9 substrates phenytoin and losartan, alone and in combination, in a study of 16 healthy volunteers. Phenytoin shows a narrow therapeutic index and non-linear pharmacokinetics. Volunteers received each drug for 10 days with a three-week washout between.

Concurrent losartan did not significantly alter phenytoin's pharmacokinetics. On the other hand, concurrent phenytoin increased losartan's mean area under the concentration-time curve from time zero to 24 hours [AUC(0-24)] by 17 percent. However, this difference did not reach statistical significance.

Fourteen subjects expressed CYP2C9(*)1/(*)1. In these volunteers, losartan's mean AUC(0-24) increased by 29 percent. This difference was statistically significant.

Concurrent phenytoin reduced the AUC(0-24) for E3174, losartan's active carboxylic-acid metabolite, by 63 percent. Concurrent phenytoin also inhibited losartan's conversation to E3174 from 1.91 to 0.62 mL/h per kilogram.